We have proposed and obtained experimental results to support our theory that opiate action is mediated by 2 neuropeptide receptors in the CNS. We propose that these 2 neuropeptides (B-endorphin and ACTH --which are cleaved from the same precursor in brain and pituitary) function as an integrated neuromodulatory system, and the opiate abstinence syndrome is the result of a deranged equilibrium in this system. We further propose that opiate abstinence is due to the residual presence of the opiate at the ACTH receptor following removal (by naloxone blackade) or weakening (by tolerance development) of the inhibitory action of the endorphin receptor. If the multiple effects of opiates are indeed dissociable and mediated by separate receptors, i.e., narcotic analgesia being mediated by the endorphin receptor and narcotic dependence by the ACTH receptor, this would have profound implications for the treatment of narcotic addicts, as well as the development of a potent analgesic devoid of dependence liability.